DESCRIPTION: In the last four years, the applicant's research group has documented human telomere shortening, telomerase activation in immortalization and cancer, and established a model that is now widely being tested for the role of telomerase in tumor progression. This group further cloned the RNA component of human and mouse telomerase, and characterized the expression in normal cells and in cancer. Goals in the present application will be: i) to characterize the structure and function of the human telomerase RNA component; ii) to clone the protein components of telomerase; and iii) to determine the pathways that regulate telomerase in normal human cells. When all of the cloned components are in hand, and sufficient information has been gained concerning telomerase regulation, it should become possible to devise direct experimental tests of the role of telomerase in aging and cancer. This basic understanding is essential to evaluate the efficacy and potential toxicity of approaches that are being developed to target telomerase in anti-cancer therapies.